Open AccessTranscriptional profiling of recall responses to F rancisella live vaccine strain
Author(s) -
Paranavitana Chrysanthi,
DaSilva Luis,
Vladimirova Antoaneta,
Pittman Phillip R.,
Velauthapillai Mahendran,
Nikolich Mikeljon
Publication year - 2014
Publication title -
pathogens and disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.983
H-Index - 105
ISSN - 2049-632X
DOI - 10.1111/2049-632x.12113
Subject(s) - biology , immunology , antigen presentation , immune system , francisella tularensis , memory b cell , antigen , antigen processing , dendritic cell , t cell , b cell , antibody , gene , genetics , virulence
Global gene expression profile changes were monitored in human peripheral blood mononuclear cells ( PBMC s) after challenge with the live vaccine strain ( LVS ) of Francisella tularensis . Because these PBMC s were from individuals previously immunized with LVS , stimulating these cells with LVS should activate memory responses. The Ingenuity Pathway Analysis tool identified pathways, functions, and networks associated with this in vitro recall response, including novel pathways triggered by the memory response. Dendritic cell (DC) maturation was the most significant among the more than 25 relevant pathways discovered. Interleukin 15, granulocyte–macrophage colony‐stimulating factor, and triggering receptor expressed on myeloid cells 1 signaling pathways were also significant. Pathway analysis indicated that Class 1 antigen presentation may not be optimal with LVS vaccination. The top three biological functions were antigen presentation, cell‐mediated and humoral immune responses. Network analysis revealed that the top network associated with these functions had IFN γ and TNF α in central interactive positions. Our results suggest that DC maturation is a key factor in the recall responses and that more effective antigen processing and presentation is needed for cytotoxic T lymphocyte responses. Taken together, these considerations are critical for future tularemia vaccine development studies.